Early occurrence of metastatic differentiated thyroid carcinomas in transgenic mice expressing the A2a adenosine receptor gene and the human papillomavirus type 16 E7 oncogene

摘要: We report here the characterization of a transgenic mouse model (Tg-A2aR/Tg-E7) resulting from coexpression two oncogenic transgenes in thyroid. The (Tg-A2aR and Tg-E7) were placed under control thyroid specific thyroglobulin gene promoter, directed expression either A2a adenosine receptor that constitutively activates cAMP pathway, or E7 protein human papillomavirus type 16, binds inactivates retinoblastoma susceptibility product (Rb1). Transgenic mice expressing both generated by interbreeding Tg-A2aR Tg-E7 lines, characterized previously (Ledent et al., 1992, 1995). These develop larger goiter than parental severe hyperthyroidism comparable to observed line. main feature Tg-A2aR/Tg-E7 is rapid occurrence malignant lesions, dissemination tissue through blood stream, generating multiple differentiated functional metastases lung. appeared as early 2 months after birth their frequency increased 75% over 3 months. They associated with presence large vascular lakes Electron microscopy cells revealed nuclear features similar those papillary carcinoma. mice, which oncogenes are co-expressed thyroid, represent first genetic animal developing metastatic carcinomas high frequency.